Document Detail


CD74 and macrophage migration inhibitory factor as therapeutic targets in gastric cancer.
MedLine Citation:
PMID:  22611320     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: To investigate the relationship and molecular features of CD74/macrophage migration inhibitory factor (MIF)/Toll-like receptor 4 (TLR4) in gastric cancer.
METHODS: CD74, MIF and TLR4 expression in the paraffin-embedded sections of gastric cancer from 120 patients were detected by immunohistochemical staining. Knock down of CD74 expression in gastric cancer cell line MKN-45 was performed by lentivirus transduction and detected by Western blotting. MKN-45 cell proliferation assay under the stimulants was measured by the cell counting kit 8 (CCK8) assay and MIF concentration in the culture medium was detected by enzyme-linked immunosorbent assay. Surface staining of CD74 in the MKN-45 cell line under the stimulation of lipopolysaccharide (LPS) was measured by flow cytometry. MIF, CD74 and TLR4 co-localization in the MKN-45 cell line was performed by the immunoprecipitation.
RESULTS: CD74, MIF and TLR4 were found to be expressed in gastric cancer and increased significantly in the advanced stage, and were also associated with lymph node metastasis. Correlation analysis revealed that CD74 was positively correlated with MIF (r = 0.2367, P < 0.01) and both proteins were also associated with TLR4 (r = 0.4414, r = 0.5001, respectively, P < 0.01). LPS can significantly promote MKN-45 cell proliferation (3.027 ± 0.388 vs 4.201 ± 0.092, P < 0.05), induce MIF production (54.333 ± 2.906 pg/mL vs 29.667 ± 3.180 pg/mL, P < 0.01) and cell surface expression of CD74 (75.6% ± 4.046% vs 9.4% ± 0.964%, P < 0.01) at LPS concentration of 1 μg/mL compared to medium control. Knockdown of CD74 or using anti-CD74 and MIF antagonist ISO-1 significantly reduced LPS-induced MKN-45 cell proliferation (4.201 ± 0.092 vs 3.337 ± 0.087, 4.534 ± 0.222 vs 3.368 ± 0.290, 4.058 ± 0.292 vs 2.934 ± 0.197, respectively, P < 0.01). MIF, CD74 and TLR4 could co-localize in the MKN-45 cell line.
CONCLUSION: Upregulation of MIF, CD74 and TLR4 are associated with increasing clinical stage and provide an opportunity as novel gastric cancer chemoprevention and/or treatment strategy.
Authors:
Ying-Xia Zheng; Ming Yang; Ting-Ting Rong; Xiang-Liang Yuan; Yan-Hui Ma; Zhi-Hao Wang; Li-Song Shen; Long Cui
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  World journal of gastroenterology : WJG     Volume:  18     ISSN:  1007-9327     ISO Abbreviation:  World J. Gastroenterol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-21     Completed Date:  2012-09-17     Revised Date:  2013-06-24    
Medline Journal Info:
Nlm Unique ID:  100883448     Medline TA:  World J Gastroenterol     Country:  China    
Other Details:
Languages:  eng     Pagination:  2253-61     Citation Subset:  IM    
Affiliation:
Department of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Differentiation, B-Lymphocyte / genetics,  metabolism*
Blotting, Western
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Gene Knockdown Techniques
Histocompatibility Antigens Class II / genetics,  metabolism*
Humans
Immunohistochemistry
Immunoprecipitation
Intramolecular Oxidoreductases / antagonists & inhibitors,  metabolism*
Isoxazoles / pharmacology
Lipopolysaccharides / pharmacology
Lymphatic Metastasis
Macrophage Migration-Inhibitory Factors / antagonists & inhibitors,  metabolism*
Male
Middle Aged
Neoplasm Staging
Stomach Neoplasms / genetics,  immunology*,  pathology,  therapy
Toll-Like Receptor 4 / metabolism
Up-Regulation
Chemical
Reg. No./Substance:
0/3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester; 0/Antigens, Differentiation, B-Lymphocyte; 0/Histocompatibility Antigens Class II; 0/Isoxazoles; 0/Lipopolysaccharides; 0/Macrophage Migration-Inhibitory Factors; 0/TLR4 protein, human; 0/Toll-Like Receptor 4; 0/invariant chain; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.2.1/MIF protein, human
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